Activated protein C (APC) is an important regulatory protein that helps maintain the balance of procoagulant and anticoagulant properties within the circulation. It acts by cleaving activated factor V and activated factor VIII, limiting clot formation at the appropriate level. An abnormal factor V that is resistant to cleavage by APC has been described recently in patients with venous thrombosis. We have set up an assay using DNA amplification of the portion of the factor V gene responsible for its resistance to APC. An abnormal cleavage pattern of the DNA product is seen using a restriction enzyme in patients with this mutation, which can be correlated with a functional (clotting) assay to screen patients at risk for or with a history of venous thromboembolism.